Serum Electrolytes in Neonates With Moderate and Severe Hypoxic Ischaemic Encephalopathy on Therapeutic Hypothermia at Kenyatta National Hospital

Abstract

Background Hypoxic Ischaemic Encephalopathy (HIE) is a birth complication affecting full term infants. Globally, it contributes to significant morbidity and mortality in newborns. In the developed world, the incidence of HIE is estimated at 1-8 per 1000 live births as compared to 26 per 1,000 in the developing world. HIE contributes significantly to morbidity and mortality in infants less than 24 months of age with more than 40% dying or developing severe neurological deficits. Therapeutic hypothermia is the only current proven neuroprotective therapy for treatment of moderate and severe HIE. It is initiated within the first six hours of life and has three phases; induction, cooling and rewarming. Core body temperature is maintained for 72 hours at 33℃ to 35°C. This study aims to establish the serum sodium, calcium and potassium levels in babies with moderate and severe HIE and to compare these electrolyte levels with babies with moderate to severe HIE not undergoing Therapeutic Hypothermia at KNH. The results will inform better monitoring and care of these babies. There is paucity of literature on electrolyte disturbances associated with Therapeutic Hypothermia and findings from this study will add to this information. Objectives To determine the effect of Therapeutic Hypothermia on sodium, calcium and potassium levels in neonates with moderate and severe HIE in Kenyatta National Hospital Methods A prospective cohort study was conducted on 74 neonates with moderate and severe HIE admitted to KNH NBU. The cases, chosen using consecutive sampling were 37 neonates with moderate and severe HIE admitted to the KNH Newborn unit (NBU) who received Therapeutic hypothermia while the controls were 37 age and degree of HIE matched term neonates who were not cooled due to the limited number of cooling devices available at KNH NBU. Participants were identified using a predetermined inclusion and exclusion criteria. Informed consent was obtained. Serum electrolytes (sodium, calcium and potassium) were measured on day 1(baseline), day 2(Cooling phase) and day 4 (rewarming phase) of life. Data Analysis Data analysis was then done using R Software version 4.2.2. Inferential analysis was done on the trend of the electrolytes across the cooling and rewarming phase using paired T test. Further analysis was done where day 1 ,2 and 4 Calcium, Potassium and Sodium values for both groups were analysed using the 2 sample T test for between group differences. The results were presented as summary statistics, tables and graphs. Ethical Considerations The investigator did not assign subjects into the respective groups. The subjects in the control group were infants who met the criteria for Therapeutic Hypothermia but did not receive the intervention due to the limited number of cooling devices available at KNH NBU. X Results 74 neonates were enrolled into the study with 37 receiving Therapeutic Hypothermia and 37 in the control group. In the group undergoing Therapeutic hypothermia, at baseline, the mean calcium level was 1.99mmol/L (SD 0.19), sodium 131.62mmol/L (SD 6.59) and potassium 5.72 mmol/L (SD 1.11) In the cooling phase, there was a statistically significant increase in calcium, mean difference 0.16mmo/l (p<0.0001). For potassium, the mean difference was -1.09 mmol/L (p < 0.0001), indicating a statistically significant decrease. In contrast, the mean difference for sodium was 0.89 mmol/L, but the p-value was not significant (p = 0.5). In the rewarming phase, the mean difference for calcium was 0.2 mmol/L (p < 0.0001), indicating a statistically significant increase. For potassium, the mean difference was -0.36 mmol/L (p = 0.0113), indicating a statistically significant decrease. The mean difference for sodium was 3.1 mmol/L (p = 0.0008), which was also statistically significant, indicating a substantial increase in sodium levels during the rewarming phase compared to the cooling phase. Overall neonates undergoing therapeutic hypothermia had higher mean calcium and sodium levels with lower mean potassium levels from baseline during both cooling and rewarming phases, with more significant changes in the latter. In the Therapeutic Hypothermia group, hypocalcemia (72.9%), hyperkalemia (48.6%) and hyponatremia (35.1%) were reported on day 1 of life. The incidence of hypocalcemia reduced from 72.9% before TH to 5.4% after TH, hyponatremia reduced from 35.1%% before TH to 0% after TH and hyperkalemia a reduced from 48.6% before TH to 2.7% after TH. In this study, Therapeutic hypothermia did not result in significant further derangements of sodium, calcium and potassium levels from baseline. There was no significant difference in sodium and potassium levels in the TH group compared to the non-TH group. However, the incidence of hypocalcemia was higher in the non-TH group (29.7%) compared to the TH group (5.4%). Here the difference between the two groups was statistically significant with a p value of 0.0043 and an odds ratio of 0.15 (95% Confidence Interval 0.01 – 0.94). Conclusions At baseline, both the TH and no TH groups had deranged serum electrolytes (hyperkalemia, hyponatremia and hypocalcemia). This indicates that Perinatal asphyxia causes derangements in these electrolytes. Therapeutic Hypothermia was not found to have further adverse derangements in sodium, potassium and calcium levels from baseline and has been associated with lower incidence of hypocalcemia, hyperkalemia and hyponatremia Recommendations All infants with moderate and severe HIE should have serum electrolytes monitored whether on Therapeutic Hypothermia or not